Human immunodeficiency virus (HIV) is a type of RNA virus. The surface of the virus is a bilayer lipid membrane. The membrane envelops therein 2 single stranded RNA and some important enzymes (such as reverse transcriptase, protease, integrase) and structural proteins (p24, p17, p7 and etc.). There are two very important glucoproteins gp120 and gp41 on the membrane surface of the virus. gp120 lies in the exterior of the membrane, and gp41 crosses over the bilayer lipid membrane and forms together with gp120 a composite. Their main function is to identify and attach the cells having CD4 surface receptor, for example, lymphocytes (T cells), macrophages and etc., in human immune system. HIV cannot reproduce in vitro, but can only replicate and regenerate by the aid of human cells. The replication process of HIV may be roughly divided into the following stages: binding and fusion of virus and host cells; reverse transcription, integration, transcription and translation of virus gene; assembly and release of virus. HIV virus is continuously replicated according to such a cycle process, to infect human immunocytes and destroy human immune system, which finally leads to the complete loss of human immune function, so that the patients are in the risk of various infections without any resisting ability. In theory, any drug, only if it blocks a link in the replication process of virus, can fulfill the purpose of inhibiting virus and treating diseases.
Until now, there are more than 30 types of chemical drugs and combinations thereof useful for resisting HIV infection and treating AIDS in clinical on the market. According to their action mechanism, the existing drugs are divided into the following five types: nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (Enfuvirtide) and entry inhibitors (Maraviroc). The existing drugs used alone or in combination can effectively inhibit the replication of virus in vivo, but the main problem that all of them are confronted with is drug resistance. After acting with drug for a certain period of time, HIV virus may have some kind of variation. Variant virus can be free from the inhibition of drug, and, just like the case before medication, a large quantity of viruses continue to be replicated in vivo. Therefore, it has always been a hot spot in the field of drug research in recent years to search and develop a new generation of anti-AIDS drugs having new structure type, new action mechanism, new target site or protent inhibitory effect on drug-resistant virus.
Up to now, there are four non-nucleoside reverse transcriptase inhibitors [Nevirapine, Delavirdine, Efavirenz, Entravine] on the market. This type of drugs have various advantages including structure diversity, high efficiency, low toxicity, clear target site and action mechanism, noncompetitive inhibitors and etc., and play an important role in anti-HIV combination therapy (HAART). However, the problems associated with these drugs mainly include that the virus is easy to produce drug resistance or the drugs are taken at a relatively high frequency every day. In order to overcome the drawbacks of the existing drugs, it is necessary to search for a new generation of drugs as inhibitors of non-nucleoside reverse transcriptase, which are capable of effectively inhibiting the replication of wild type and multidrug-resistant HIV virus strains.